TRANSDERMAL HORMONAL

CONTRACEPTION Prof. Aboubakr Elnashar

Benha University Hospital, Egypt Email: elnashar53@hotmail.com

Aboubakr Elnashar

Missed pills 50% of pill users missed 3 pills/pack by the 3rd cycle of

oral contraceptive use (Potter et al.,2001)

Aboubakr Elnashar

Contents •Advantages

•Formulations

Description of the Patch

Instruction for use

Patch adhesion

Pharmakokinetics

Side effects

Contraindication

Patient satisfaction

Compliance

Efficacy

Conclusion

Aboubakr Elnashar

Advantages (Burkman, 2007)

Continuous, sustained release:

avoids peak& low drug levels

Longer dosing interval:

improves patient compliance

Avoids first-pass:

met& enzymatic degradation by GIT induction of hepatic protein synthesis e.g. extrinsic clotting factors.

Aboubakr Elnashar

TD:

Can be given when oral route is not suitable

Unaffected by vomiting or diarrhea.

Drug administration stops with patch removal

Aboubakr Elnashar

Formulations ORTHO EVRA: FDA 2001 0.75 mg EE

6.0 mg norelgestromin: active metabolite of

norgestimate: (Cilest: EE, 30ug, Norgestimate, 250 Ug)

Aboubakr Elnashar

EVRA 0.6 mg EE

6.0 mg Norelgestromin

Daily delivery

rate

150 ug

NGMN

20 ug

EE

Aboubakr Elnashar

Mode of action •Suppress

ovulation similar to OCs.

follicular development.

•Reduce cervical mucus scores, more hostile to

sperm penetration.

•Induce progestational endometrium and reduce

endometrial thickness.

Aboubakr Elnashar

Description of the Patch 3 separate layers:

Lower: packing, light brown,

flexible 4.5 x 4.5 cm

Middle: adhesive, contains the

active hormones

Top: protecting the adhesive layer

& removed prior to application

Aboubakr Elnashar

Instruction for use

4 sites:

Upper Torso

(excluding the breasts)

Upper outer arm

Lower abdomen

Buttock

Two consecutive patches should not be placed over

the exact same area.

Hormonal absorption from the lower abdomen is 20%

lower than that from the other 3 sites

Aboubakr Elnashar

Regimen:

• One patch/w for 3ws, followed by a patch-free w.

• The first patch should be placed on 1st day of the

menstrual cycle

• If a patch change is missed for 2 d:

clinical efficacy is maintained: backup contraception

is not needed.

Aboubakr Elnashar

When initiating: • After childbirth and no-breast feeding: Wait 4 w

Backup contraception for 7 days.

• After a first-trimester miscarriage: immediately (the same day).

Backup contraception is not necessary if the patch is

started within 5 days.

Aboubakr Elnashar

Patch adhesion Patch to the abdomen (Zacur et al, 2002)

Showers, sunbathing, strenuous exercise, sauna,

whirlpool, treadmill, swimming:

Adhesive reliability was maintained for 7 d

1.8%: replaced {fell off} 2.9%: replaced {partial detachment }

Aboubakr Elnashar

Pharmakokinetics ORTHO EVRA patch Vs OCs (FDA)

1. Higher EE steady concentrations: AUC & average concentration at steady state for EE

are 60% higher

2. lower EE peak concentrations. 25%

Increased estrogen exposure: increase the risk of

adverse events, including VTE.

Aboubakr Elnashar

Aboubakr Elnashar

3. Coagulation factors

(antithrombin III, tProtS and fProtS): No significant differences (Johnson et al, 2006).

Higher EE levels seen with the patch

might not have any greater hepatic impact than lower

EE levels seen with the pill.

Aboubakr Elnashar

Side effects 1. VTE Jick et al, 2006, 2007, 2010 Risk is similar to that for users of OCs

Cole et al, 2007: increased risk of with the patch Vs OCs

VTE /100,000 women years:

Patch: 40.8

OCs: 18.3

Aboubakr Elnashar

little or no increased VTE Contraindicated: in high risk for VTE: Safe

Aboubakr Elnashar

2. Headache& nausea:

The most frequent adverse events (Sibai et al, 2002)

Aboubakr Elnashar

3. Breast symptoms: (discomfort, engorgement, pain)

more with patch than OCs during cycles 1& 2 only

with continued use, decreased to none during cycle

13 (Sibai et al, 2002)

Aboubakr Elnashar

4. Dysmenorrhea greater in patch than in OC users

(13.3% Vs 9.6%) (Sibai et al, 2002)

5. BTB: Low& similar to those with OCs (Zieman et al, 2002).

Aboubakr Elnashar

6. Application site reactions Mild or moderate

20%

Discontinuation: 2.6% (Sibai et al, 2002)

Aboubakr Elnashar

7. Changes in wt. Minimal

Use for 13 cycles:

2.2%: wt gain of 10%

1.4%: wt loss of 10%.

Comparable to OCs (Sibai et al, 2002)

With the exception of application site reactions,

patch is well tolerated

adverse events are similar to that of OCs.

Aboubakr Elnashar

Aboubakr Elnashar

Contraindications • Identical to those for OCs

• Exceptions.

1. Active skin conditions: which could alter the rate

of hormonal absorption

2. Dermatologic conditions that would be worsened

by patch application.

• On the other hand

patches are used when pills can not be used e.g. GIT

absorption problems

Aboubakr Elnashar

Patient satisfaction Emotional

Physical well-being Improvements in premenstrual symptoms Higher than OCs (Urdl et al, 2005).

: Significantly better compliance: fewer unintended pregnancies

European multinational study (2011)

High levels of women's satisfaction and

compliance with TD contraception

Aboubakr Elnashar

Compliance Consistent & correct use

(89% Vs. 79%). Compliance was higher for the patch (Cochrane systematic review, Gallo et al, 2003; Audet et al, 2001)

Aboubakr Elnashar

Efficacy Overall& method failure: Method failure: 0.4 % User failure: 0.1% Efficacy:

Higher {higher rates of correct& consistent use of

patch}

Similar (Cochrane systematic review, Gallo et al, 2003)

less effective

Wt >90 kg (Zieman et al, 2002)

Aboubakr Elnashar

Conclusion TD C patch compared to COs:

Similar efficacy& adverse effects

Higher satisfaction & compliance

Easier to use

More suitable for today’s active lifestyles

Aboubakr Elnashar

Benha University Hospital, Egypt

Email: elnashar53@hotmail.com

Prof. Aboubakr Elnashar

Aboubakr Elnashar